Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin.

Aims: Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycaemia in patients with type 2 diabetes (T2DM) by increasing urinary glucose excretion. Owing to its mechanism of action, dapagliflozin could potentially affect the renal tubular transportation of bone minerals. Therefore, markers of bone formation and resorption and bone mineral density (BMD) were evaluated in patients with T2DM after 50 weeks of dapagliflozin treatment.

The effect of continuous positive airway pressure usage on sleepiness in obstructive sleep apnoea: real effects or expectation of benefit?

Rationale: Placebo responses are complex psychobiological phenomena and often involve patient expectation of benefit. With continuous positive airway pressure (CPAP) treatment of obstructive sleep apnoea, greater hours of CPAP use are associated with reduced sleepiness. However, these open-label studies have not controlled for patient expectation of benefit derived from their knowledge of hours of device use.

Effects of chronic treatment with metformin on dipeptidyl peptidase-4 activity, glucagon-like peptide 1 and ghrelin in obese patients with Type 2 diabetes mellitus.

Aims: Studies investigating the acute effects of metformin have demonstrated actions on the incretin system and appetite regulatory hormones. There are limited data to support that these effects are sustained in the long term. We therefore studied the effects of chronic treatment with metformin on endogenous glucagon-like peptide 1, dipeptidyl peptidase-4 activity and active ghrelin (an orexigenic hormone) in obese patients with Type 2 diabetes mellitus.

PPAR agonists for the treatment of cardiovascular disease in patients with diabetes.

Diabetes is a complex disease defined by hyperglycaemia; however, strong associations with abdominal obesity, hypertension and dyslipidaemia contribute to the high risk of cardiovascular disease. Although aggressive glycaemic control reduces microvascular complications, the evidence for macrovascular complications is less certain. The theoretical benefits of the mode of action of peroxisome proliferator-activated receptor (PPAR) agonists are clear.

Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin: a randomized trial.

Background: Dapagliflozin, a selective inhibitor of sodium-glucose cotransporter 2, may improve glycemic control with a lower dose of insulin and attenuate the associated weight gain in patients with inadequate control despite high doses of insulin.

Objective: To evaluate the efficacy and safety of adding dapagliflozin therapy in patients whose type 2 diabetes mellitus is inadequately controlled with insulin with or without oral antidiabetic drugs.

Design: A 24-week, randomized, placebo-controlled, multicenter trial followed by a 24-week extension period.

Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin.

Context: Dapagliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, reduces hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by increasing urinary glucose excretion, and weight loss is a consistent associated finding.

Objectives: Our objectives were to confirm weight loss with dapagliflozin and establish through body composition measurements whether weight loss is accounted for by changes in fat or fluid components.

Design And Setting: This was a 24-wk, international, multicenter, randomized, parallel-group, double-blind, placebo-controlled study with ongoing 78-wk site- and patient-blinded extension period at 40 sites in five countries.

Risk of misdiagnosis, health-related quality of life, and BMI in patients who are overweight with doctor-diagnosed asthma.

Background: Obesity and asthma both cause breathlessness, and there is a risk of misdiagnosis of asthma in patients who are obese. Impaired health-related quality of life (HRQoL) and increased BMI increase physician attendance rates, increasing this risk. We explored the possibility of misdiagnosis and the relationship between BMI, HRQoL, and other traditional measures of asthma severity in subjects who were obese with a doctor's diagnosis of asthma.

Ghrelin does not orchestrate the metabolic changes seen in fasting but has significant effects on lipid mobilisation and substrate utilisation.

Objective: Short-term fasting is associated with increased GH pulsatility and mobilisation of fats, but underlying mechanisms are unclear. We studied ghrelin's role during fasting and the effects of exogenous ghrelin on lipid mobilisation.

Design: Randomised placebo-controlled study.

The four-variable modification of diet in renal disease formula underestimates glomerular filtration rate in obese type 2 diabetic individuals with chronic kidney disease.

Aims/hypothesis: GFR is commonly estimated using the four-variable Modification of Diet in Renal Disease (MDRD) formula and this forms the basis for classification of chronic kidney disease (CKD). We investigated the effect of obesity on the estimation of glomerular filtration rate in type 2 diabetic participants with CKD.

Methods: We enrolled 111 patients with type 2 diabetes mellitus in different stages of CKD.

The relationship between measures of cognitive attention and behavioral ratings of attention in typically developing children.

In the present study, we explored the relation between performance on cognitive measures of attention (selection, sustained, and control) and behavioral ratings of inattention and hyperactivity in a sample of typically developing children aged 3 to 7 years. We also examined the influence of chronological age and IQ on both task performance and behavior ratings. Four well-documented attention paradigms were employed, the Visearch (single-target search) task as a measure of selective attention, the Continuous Performance Test (CPT) as a measure of sustained attention, the Day-Night task as a measure of response inhibition, and the Visearch (dual-target search) task as a measure of inhibitory control.

Charting the developmental trajectories of attention and executive function in Chinese school-aged children.

Attention is a complex domain that has reawakened research interest in recent years. There are relatively few studies that have examined age-related changes across different attention subcomponents, such as selection, maintenance, and control, using large samples covering a wide age range. The present study assessed performance in 466 participants in order to identify the ages at which mature performance was reached across differing attention subcomponents.

Replication error deficient and proficient colorectal cancer gene expression differences caused by 3'UTR polyT sequence deletions.

Replication error deficient (RER+) colorectal cancers are a distinct subset of colorectal cancers, characterized by inactivation of the DNA mismatch repair system. These cancers are typically pseudodiploid, accumulate mutations in repetitive sequences as a result of their mismatch repair deficiency, and have distinct pathologies. Regulatory sequences controlling all aspects of mRNA processing, especially including message stability, are found in the 3'UTR sequence of most genes.

Human RBP4 adipose tissue expression is gender specific and influenced by leptin.

Objective: The role of retinol-binding protein-4 (RBP4) in human insulin resistance remains controversial, which may in part be explained by a gender-specific secretion of RBP4 in adipose tissue (AT). The aim of the study was to determine gender-specific depot expression of RBP4 and to identify metabolic parameters and cytokines/adipokines associated with RBP4.

Research Design And Methods: The study is an ex-vivo prospective analysis of paired AT-samples from 22 men and 26 women of similar age [men: 43·4 ± 13 (mean ± SD)years, women: 44·1 ± 12 years], BMI (men: 41·9 ± 18kg/m(2) , women: 38·4 ± 11kg/m(2) ) and homeostasis model assessment of insulin resistance taken during elective surgery and ex-vivo culture using visceral-AT (VAT)-explants (n = 10).

Ghrelin inhibits autonomic function in healthy controls, but has no effect on obese and vagotomized subjects.

Objective: Ghrelin inhibits sympathetic nervous system (SNS) activity in rodents. We studied the effect of ghrelin on healthy humans, in obesity and in vagotomized subjects.

Design: Randomized, double-blinded, placebo-controlled crossover.

Development of a vocabulary of object shapes in a child with a very-early-acquired visual agnosia: a unique case.

We report a longitudinal study of an exceptional child (S.R.) whose early-acquired visual agnosia, following encephalitis at 8 weeks of age, did not prevent her from learning to construct an increasing vocabulary of visual object forms (drawn from different categories), albeit slowly.

Nurse-led clinics for strict hypertension control are effective long term: a 7 year follow-up study.

Aims: The primary aim was to assess long-term blood pressure in 110 patients with Type 2 diabetes who had achieved optimal blood pressure control during attendance at a protocol-based nurse-led hypertension intensive intervention clinic 7 years previously. The secondary aim was to assess modifiable cardiovascular risk factor status.

Methods: One hundred and ten patients who attended the clinic during 2000-2002 were selected to reattend to have their blood pressure measured to the same standard as it was during the intensive intervention clinic, by the same specialist nurse.

Absence of insulin signalling in skeletal muscle is associated with reduced muscle mass and function: evidence for decreased protein synthesis and not increased degradation.

Loss of skeletal muscle mass and function is observed in many insulin-resistant disease states such as diabetes, cancer cachexia, renal failure and ageing although the mechanisms for this remain unclear. We hypothesised that impaired insulin signalling results in reduced muscle mass and function and that this decrease in muscle mass and function is due to both increased production of atrogenes and aberrant reactive oxygen species (ROS) generation. Maximum tetanic force of the extensor digitorum longus of muscle insulin receptor knockout (MIRKO) and lox/lox control mice was measured in situ.

In humans the adiponectin receptor R2 is expressed predominantly in adipose tissue and linked to the adipose tissue expression of MMIF-1.

In this study, the regional adipose tissue-adiponectin (AT-ADN) and adiponectin receptor (R1 and R2) expression and their relation with metabolic parameters, circulating and AT-derived cytokine expressions were compared. Paired subcutaneous adipose tissue (SCAT) and visceral adipose tissue (VAT) were taken from 18 lean and 39 obese humans, AT-mRNA expression of adipokines analysed by RT-PCR and corresponding serum levels by enzyme-linked immunosorbent assay (ELISA). R1 and R2 adipocyte expression was compared with 17 other human tissues.

SPARC: a key player in the pathologies associated with obesity and diabetes.

SPARC (secreted protein acidic and rich in cysteine, also known as osteonectin or BM-40) is a widely expressed profibrotic protein with pleiotropic roles, which have been studied in a variety of conditions. Notably, SPARC is linked to human obesity; SPARC derived from adipose tissue is associated with insulin resistance and secretion of SPARC by adipose tissue is increased by insulin and the adipokine leptin. Furthermore, SPARC is associated with diabetes complications such as diabetic retinopathy and nephropathy, conditions that are ameliorated in the Sparc-knockout mouse model.

Cancer stem cells from colorectal cancer-derived cell lines.

Cancer stem cells (CSCs) are the subpopulation of cells within a tumor that can self-renew, differentiate into multiple lineages, and drive tumor growth. Here we describe a two-pronged approach for the identification and characterization of CSCs from colorectal cancer cell lines, using a Matrigel-based differentiation assay, and cell surface markers CD44 and CD24. About 20 to 30% of cells from the SW1222 cell line form megacolonies in Matrigel that have complex 3D structures resembling colonic crypts.

Mitochondria as a source of mechanical signals in cardiomyocytes.

Aims: The myofibrillar and nuclear compartments in cardiomyocytes are known to be sensitive to extracellular mechanical stimuli. Recently, we have shown that alterations in the mitochondrial ionic balance in cells in situ are associated with considerably increased mitochondrial volume. Theoretically, this swelling of mitochondria could impose mechanical constraints on the myofibrils and nuclei in their vicinity.